Having established the chimpanzee as an animal model for HIV infection, in the second phase of our studies, emphasis is being placed on establishing a reproducible disease model for AIDS. To induce clinical manifestations, conditions simulating the human experience have been employed, namely repeated inoculation of virus, coinfection with other viruses, and immunologic stimulation. In the second phase of this study, we attempted to induce a reproducible disease model and to assess the parameters in addition to HIV, which may be essential to disease development. We have evaluated the use of repeated virus inoculation and the effect of repeated antigenic stimulation primarily in the form of factor VIII concentrates. We also have looked at the effect of simultaneous CMV, HBV and NANBV infection. None of these manipulations has resulted in a consistent disease model. In the next phase of studies we are going to continue frequent virus administration but are going to add large volume allogeneic stimulation by the cross-transfusion of allogenic lymphocytes that contain class I and class 11 determinants. We also are going to treat the lymphocytes in vitro with IL-2 and give bolus IL-2 to the chimp. In addition we are using the chimpanzee model to assess the early events of HIV infection and to determine if any new test parameters can narrow early window of HIV infections.